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HIV-1 Nef Inhibits Protease Activity and Its Absence Alters Protein Content of Mature Viral Particles
Nef is an important player for viral infectivity and AIDS progression, but the mechanisms involved are not completely understood. It was previously demonstrated that Nef interacts with GagPol through p6*-Protease region. Because p6* and Protease are involved in processing, we explored the effect of...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3991643/ https://www.ncbi.nlm.nih.gov/pubmed/24748174 http://dx.doi.org/10.1371/journal.pone.0095352 |
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author | Mendonça, Luiza M. Poeys, Sandro C. Abreu, Celina M. Tanuri, Amilcar Costa, Luciana J. |
author_facet | Mendonça, Luiza M. Poeys, Sandro C. Abreu, Celina M. Tanuri, Amilcar Costa, Luciana J. |
author_sort | Mendonça, Luiza M. |
collection | PubMed |
description | Nef is an important player for viral infectivity and AIDS progression, but the mechanisms involved are not completely understood. It was previously demonstrated that Nef interacts with GagPol through p6*-Protease region. Because p6* and Protease are involved in processing, we explored the effect of Nef on viral Protease activity and virion assembly. Using in vitro assays, we observed that Nef is highly capable of inhibiting Protease activity. The IC50 for nef-deficient viruses in drug susceptibility assays were 1.7- to 3.5-fold higher than the wild-type counterpart varying with the type of the Protease inhibitor used. Indicating that, in the absence of Nef, Protease is less sensitive to Protease inhibitors. We compared the protein content between wild-type and nef-deficient mature viral particles by gradient sedimentation and observed up to 2.7-fold reduction in the Integrase levels in nef-deficient mature particles. This difference in levels of Integrase correlated with the difference in infectivity levels of wild type and nef-deficient viral progeny. In addition, an overall decrease in the production of mature particles was detected in nef-deficient viruses. Collectively, our data support the hypothesis that the decreased infectivity typical of nef-deficient viruses is due to an abnormal function of the viral Protease, which is in turn associated with less mature particles being produced and the loss of Integrase content in these particles, and these results may characterize Nef as a regulator of viral Protease activity. |
format | Online Article Text |
id | pubmed-3991643 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39916432014-04-21 HIV-1 Nef Inhibits Protease Activity and Its Absence Alters Protein Content of Mature Viral Particles Mendonça, Luiza M. Poeys, Sandro C. Abreu, Celina M. Tanuri, Amilcar Costa, Luciana J. PLoS One Research Article Nef is an important player for viral infectivity and AIDS progression, but the mechanisms involved are not completely understood. It was previously demonstrated that Nef interacts with GagPol through p6*-Protease region. Because p6* and Protease are involved in processing, we explored the effect of Nef on viral Protease activity and virion assembly. Using in vitro assays, we observed that Nef is highly capable of inhibiting Protease activity. The IC50 for nef-deficient viruses in drug susceptibility assays were 1.7- to 3.5-fold higher than the wild-type counterpart varying with the type of the Protease inhibitor used. Indicating that, in the absence of Nef, Protease is less sensitive to Protease inhibitors. We compared the protein content between wild-type and nef-deficient mature viral particles by gradient sedimentation and observed up to 2.7-fold reduction in the Integrase levels in nef-deficient mature particles. This difference in levels of Integrase correlated with the difference in infectivity levels of wild type and nef-deficient viral progeny. In addition, an overall decrease in the production of mature particles was detected in nef-deficient viruses. Collectively, our data support the hypothesis that the decreased infectivity typical of nef-deficient viruses is due to an abnormal function of the viral Protease, which is in turn associated with less mature particles being produced and the loss of Integrase content in these particles, and these results may characterize Nef as a regulator of viral Protease activity. Public Library of Science 2014-04-18 /pmc/articles/PMC3991643/ /pubmed/24748174 http://dx.doi.org/10.1371/journal.pone.0095352 Text en © 2014 Mendonça et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Mendonça, Luiza M. Poeys, Sandro C. Abreu, Celina M. Tanuri, Amilcar Costa, Luciana J. HIV-1 Nef Inhibits Protease Activity and Its Absence Alters Protein Content of Mature Viral Particles |
title | HIV-1 Nef Inhibits Protease Activity and Its Absence Alters Protein Content of Mature Viral Particles |
title_full | HIV-1 Nef Inhibits Protease Activity and Its Absence Alters Protein Content of Mature Viral Particles |
title_fullStr | HIV-1 Nef Inhibits Protease Activity and Its Absence Alters Protein Content of Mature Viral Particles |
title_full_unstemmed | HIV-1 Nef Inhibits Protease Activity and Its Absence Alters Protein Content of Mature Viral Particles |
title_short | HIV-1 Nef Inhibits Protease Activity and Its Absence Alters Protein Content of Mature Viral Particles |
title_sort | hiv-1 nef inhibits protease activity and its absence alters protein content of mature viral particles |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3991643/ https://www.ncbi.nlm.nih.gov/pubmed/24748174 http://dx.doi.org/10.1371/journal.pone.0095352 |
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